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    Suppression of Slit2/Robo1 mediated HUVEC migration by Robo4.
    Biochem Biophys Res Commun 2016 Jan 20;469(4):797-802. Epub 2015 Dec 20.
    Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. Electronic address:
    Slit proteins and their receptors, the Roundabout (Robo) family, are known to have a pivotal role in the vascular system. Slit2/Robo1 regulates the migration of human umbilical vein endothelial cells (HUVECs) and tumor-associated endothelial cells. Robo4, the endothelial-specific Robo, is also considered to be involved in vascular cell migration. However, the Slit/Robo signaling pathway is still unclear. Using a Boyden chamber assay, we found that Slit2 induces the migration of HUVECs under a Robo4 knockdown condition. This effect disappeared in Robo1 knockdown cells. The co-existence of the N-terminal extracellular portion of Robo1 blocked the Slit2-evoked migration of HUVECs, while that of Robo4 caused no effect. These results show that the Slit2 signal is transduced through Robo1, while the negative regulation of Robo4 is an intracellular event. Targeted proteomics using an anti-Robo1 monoclonal antibody identified CdGAP, an adhesion-localized Rac1-and Cdc42-specific GTPase activating protein, as a candidate for Slit2/Robo1 signaling. Robo1 and CdGAP were co-immunoprecipitated from CHO cells co-transfected with Robo1 and CdGAP genes. These results suggest that Slit2/Robo1 binding exerts an effect on cell migration, which is negatively regulated by Robo4, and Robo1 may function by interacting with CdGAP in HUVECs.

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    Molecular Angiogenesis Group, Cancer Research UK, Institute of Molecular Medicine, University of Oxford, Oxford, UK.
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    Exp Eye Res 2010 Jun 16;90(6):742-9. Epub 2010 Mar 16.
    Department of Ophthalmology, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China.
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    BMC Cell Biol 2008 Nov 3;9:61. Epub 2008 Nov 3.
    Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
    Background: Roundabouts are axon guidance molecules that have recently been identified to play a role in vascular guidance as well. In this study, we have investigated gene knockdown analysis of endothelial Robos, in particular roundabout 4 (robo4), the predominant Robo in endothelial cells using small interfering RNA technology in vitro.

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    J Immunol 2014 Jan 22;192(1):385-93. Epub 2013 Nov 22.
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